Org. Synth. 1970, 50, 94
[Cyclopropanecarboxylic acid, 2-phenyl-, cis-]
Submitted by Carl Kaiser, Joseph Weinstock1
, and M. P. Olmstead.
Checked by William E. Parham, Wayland E. Noland, Paul Cahill, and Thomas S. Straub.
Caution! Benzene has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving benzene should be carried out in a well-ventilated hood, and glove protection is required.
A. Ethyl cis- and trans-2-phenylcyclopropanecarboxylate
. Xylene (500 ml.
, (Note 1)
) is heated to reflux in a 2-l. flask equipped with a mechanical stirrer, dropping funnel, and reflux condenser
. A solution of 179 g. (1.57 moles) of ethyl diazoacetate
[Org. Synth., Coll. Vol. 4, 424 (1963)
] (Note 2)
and 163 g. (1.57 moles) of styrene (Note 3)
is placed in the dropping funnel and added dropwise to the refluxing, stirred xylene
over a period of 90 minutes. After addition is complete, the solution is stirred and heated at the reflux temperature for an additional 90 minutes (Note 4)
is removed under reduced pressure, and the residual red oil is distilled through a short Vigreux column
. The fraction boiling at 85–93° (0.5 mm.)
is collected, yielding 155 g.
) of colorless product, nD26
1.5166 (Note 5)
and (Note 6)
B. cis-2-Phenylcyclopropanecarboxylic acid. A 1-l., three-necked flask equipped with a dropping funnel, stirrer, and a short Vigreux column (Note 7), to which is attached a partial take-off distilling head with reflux condenser, is charged with 155 g. (0.816 mole) of ethyl cis- and trans-2-phenylcyclopropanecarboxylate, 200 ml. of ethanol, 65 ml. of water, and 24.5 g. (0.612 mole) of sodium hydroxide pellets (Note 8). The mixture is heated at the reflux temperature for 5 hours during which time 200 ml. of ethanol is slowly distilled and replaced by an equal volume of water added through the dropping funnel. Heating is discontinued, 250 ml. of water and 150 ml. of benzene are added, and the mixture is stirred for 2–3 minutes. The layers are separated, and the aqueous layer is washed with two 50-ml. portions of benzene (Note 9).
The benzene extracts are placed in the apparatus used above, and 130 ml. of water and 13 g. (0.32 mole) of sodium hydroxide pellets are added. Benzene (200 ml.) is distilled and then the 200 ml. of ethanol obtained in the initial hydrolysis is added. The reflux-distillation process is continued for 5 hours, during which time 250 ml. of distillate is obtained. The mixture is cooled, and 65 ml. of benzene and 30 ml. of concentrated hydrochloric acid are added. The layers are separated, and the aqueous solution is washed twice with 35-ml. portions of benzene. The combined benzene extracts are concentrated and dried by distillation of 90 ml. of benzene. The hot concentrate is decanted from a trace of salt, 70 ml. of petroleum ether is added, and the resulting solution is stored overnight at 0°. Filtration of the solid from the cold petroleum ether solution and washing with a small volume of cold 50:50 benzene–petroleum ether yields 19.5–23.8 g. (14.6-20.7% based on the mixed ester used, or 38–46.4% based on the cis ester, (Note 10)) of cis-2-phenylcyclopropanecarboxylic acid, m.p. 106–109° (Note 11). An additional 2–3 g. of the cis acid may be obtained by concentrating the mother liquors to low volume, adding petroleum ether, and chilling the resulting solution for several days.
The checkers used xylene
distilled from sodium
Ethyl diazoacetate is available from Aldrich Chemical Co. Diazoacetic esters are potentially explosive and, therefore, must be handled with caution.
[See Org. Synth., Coll. Vol. 4, 424 (1963)
, b.p. 52–3° (28 mm.)
was used by the submitters. The checkers used reagent grade styrene obtained from Eastman Organic Chemicals
without further purification.
Refluxing was discontinued after nitrogen
GC of several samples of the mixed ester revealed a composition of 55–65% trans
-, 30–40% cis
-ester, and 5% impurities.
The checker obtained 204 g.
of product (68%
1.5160, with the approximate composition 39% cis
The checkers used a 50-cm. Vigreux column
The amount of base used is 0.75 mole per mole of mixed esters. This is slightly more than necessary to saponify all the trans
-ester, present. Since the trans
-ester is saponified more rapidly than the cis
-ester, this affords an effective separation of the isomer. This procedure is a modification of that of Walborsky and Plonsker.2
may be obtained from the aqueous solution in the following way. The aqueous solution is treated with 65 ml. of concentrated hydrochloric acid
, and the mixture is extracted with one 130-ml. portion of benzene
and two 20-ml. portions of benzene
. The carefully separated benzene
layers are combined and dried by distilling 100 ml. of benzene
. The resulting solution is decanted from the small amount of salt present and diluted with 200 ml. of petroleum ether
. The resulting solution is cooled at 0° overnight, and the precipitate is collected and washed with a small amount of a cold, 50:50 mixture of petroleum ether–benzene
, yielding 63–65 g.
based on trans
-ester originally present) of needles, m.p. 87–93°
. Recrystallization of this product several times from carbon tetrachloride–petroleum ether
gives the pure trans
-acid, m.p. 93°
The submitters obtained 25–28 g.
based on the mixed ester used).
Burger and Yost3
reported m.p. 106–107°
for pure cis-2-phenylcyclopropanecarboxylic acid
and m.p. 93°
for pure trans-2-phenylcyclopropanecarboxylic acid
The method described is a modification of that described by Walborsky and Plonsker.2
It is based on the more rapid hydrolysis, due to less steric hindrance, of the trans
- over the cis
-ester. The cis
-acid has also been obtained by fractional crystallization of the mixed acids.3
The present method offers a convenient preparation of cis-2-phenylcyclopropanecarboxylic acid that is amenable to large-scale work. The process above has been carried out by the submitters on a twentyfold scale with essentially the same results. The method also provides an example of the separation of two isomers based on differences in reaction rate.
Chemical Abstracts Nomenclature (Collective Index Number);
hydrochloric acid (7647-01-0)
sodium hydroxide (1310-73-2)
carbon tetrachloride (56-23-5)
ethyl diazoacetate (623-73-4)
Cyclopropanecarboxylic acid, 2-phenyl-, cis- (939-89-9)
trans-2-Phenylcyclopropanecarboxylic acid (939-90-2)
Ethyl cis- and trans-2-phenylcyclopropanecarboxylate (946-39-4)
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